Opioids and the Future of Pain Management

Illustration by Maddy Angstreich

Illustration by Maddy Andstreich

Vicodin, Demerol, OxyContin, Percocet – once among the inconspicuous painkillers that only occasionally occupied household medicine cabinets (and even then, only post-surgery or in the case of a very serious medical problem), today maintain household-name status.  They are members of the family of opioid analgesics, drugs that attach to specific receptors in the brain and help to alleviate severe pain. In addition to their analgesic effect, opioids activate central dopamine reward pathways that induce feelings of euphoria and enhanced mood, a side effect that can potentially lead to addiction. Chances are you’ve encountered one or more of these drugs, perhaps through a family member, friend, or first-hand experience. Perhaps you recognize them from the media, presented in popular music, movies, or the news. Regardless of the connotations you associate with them, these medications have emerged as key players in the field of public health, their rise in ubiquity coupled with an increasingly messy web of implications for our health and future well-being.

The United States has seen a staggering increase in both opioid prescriptions and in the rates of opioid-related overdose and death. In 2012 alone, health care providers wrote 259 million prescriptions for opioid analgesics— that is enough for every adult in the United States to have their own bottle of pills. According to the Centers for Disease Control (CDC), the number of opioid prescriptions and the number of overdose deaths involving opioids have both nearly quadrupled since 1999. Concomitant to the problem of over-prescription is the risk of pill diversion: the transfer of a legally prescribed controlled substance from the patient to another person for illicit use. Diversion has a variety of forms, such as taking unused, retained pills that were once prescribed to a family member or friend. It has become increasingly necessary to evaluate the way health care providers address pain management for their patients. The over-prescription, retention, and diversion of opioid pain medications fan the flames of this opioid epidemic, and these phenomena are often unwittingly fueled by the prescribing practices of physicians.

Opioids are frequently administered to combat acute pain (that is, pain associated with soft tissue damage and typically lasting less than 3-6 months, caused by events such as surgery, broken bones, dental work, or burns/cuts). Chronic pain, on the other hand, is often defined as pain that lasts more than 6 months, sometimes without any clear cause or initial injury. An estimated 100 million people in this country live with chronic pain – that’s almost a third of the American population. For some of these people, opioid analgesics are lifesavers. After all, chronic pain can be debilitating, and keeping that pain in check via opioid therapy can greatly improve quality of life. However, there is a lack of research to shed light on the longitudinal effects of opioid therapy for chronic pain. Currently, the American Society of Anesthesiologists recommends not prescribing opioid medications as long-term therapy for chronic, non-cancer pain until the physician has extensively discussed and clarified the potential risks, including dependence, central sleep apnea, respiratory depression, and more.

Last summer, the results of a study conducted at the University of Boulder portended the potential hyperalgesic consequences of treating chronic pain with opioids. In other words: it’s possible that, paradoxically, long-term opioid therapy prolongs and heightens sensitivity to pain. The Boulder study found that opioids such as morphine increased pain in rats. In fact, just a brief treatment with morphine starting 10 days after injury in rats lead to the release of pain signals from certain immune cells, doubling the duration of pain sensitization. Certainly we need to collect more data before making any definitive claims regarding these long-term effects; nonetheless, the implications of this study at Boulder could have dire consequences, considering the enormous number of Americans using opioids to combat conditions like chronic back pain and osteoarthritis. The recent increase of opioid prescriptions in the United States could potentially magnify the issue.

What if we had potent, alternative analgesics? The Liedtke Lab, at Duke Institute for Brain Sciences at Duke University, is making strides with that notion. Wolfgang Liedtke, MD, PhD, is the lead author of a study that developed a new class of small molecule drugs. These are labeled “dual-action” compounds because they simultaneously block two different ion channels related to pain and inflammation. The first receptor, TRPV4, is linked to joint pain; the second is receptor TRPA1, which is associated with pain and itch sensations. “Whereas initially I thought for a very short while that this might be a drawback, quite rapidly I came to see that this could be an enormous advantage,” says Dr. Liedtke, regarding this serendipitous discovery. He explains, “TRPV4 and TRPA1 are both ‘pain-TRPs’ and their simultaneous inhibition [with one type of molecule] might represent a novel and highly effective way at combating pain and inflammation, also pain in the context of nerve damage.” In theory, these compounds could prompt a cascade of studies for producing new analgesics to treat conditions such as headaches, jaw pain, osteoarthritis, nerve cell injuries, skin irritation and itching, and abdominal pain linked to the pancreas and colon.

This concept could have widespread implications for the future of pain management. It will likely take several years before these new small-molecule compounds can be proposed to the FDA, but it is a promising start. If researchers can ultimately develop a legitimate alternative to standard therapies for pain management, perhaps we’d be able to mitigate the risks associated with taking opioids, decrease the amount of superfluous opioid drugs at risk for diversion, and wage the war on pain more efficiently.  Controversy emerges namely for patients facing severe forms of chronic pain not associated with cancer or end-of-life treatment; it is important to note that for some patients, such as those suffering from cancer-related pain or receiving palliative care, narcotic drugs remain the best solution to deal with pain.

As the opioid epidemic becomes more salient, organizations such as the CDC have released new prescribing guidelines, moving hospitals and prescribers toward their implementation. There is a growing push for doctors to educate patients about opioids and to discuss all potential risks and benefits with them. Physicians have recently incorporated a variety of multimodal pain treatments as well; these may or may not use narcotics along with other types of drugs and therapies.  Dr. Liedtke predicts that someday, we will be able to eliminate our extensive reliance on opioids as we know it. “I expect [anti-TRP channel drugs] to become part of our therapeutic repertoire, thus diminishing the need for classic opioids.” While opioid therapy will remain necessary for certain patients and certain diagnoses, research like that being done in the Liedtke lab sheds hopeful light for the millions of people burdened by chronic nonmalignant pain.




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